1383787-81-2Relevant articles and documents
Diphenylpyridylethanamine (DPPE) derivatives as cholesteryl ester transfer protein (CETP) inhibitors
Harikrishnan, Lalgudi S.,Finlay, Heather J.,Qiao, Jennifer X.,Kamau, Muthoni G.,Jiang, Ji,Wang, Tammy C.,Li, James,Cooper, Christopher B.,Poss, Michael A.,Adam, Leonard P.,Taylor, David S.,Chen, Alice Ye A.,Yin, Xiaohong,Sleph, Paul G.,Yang, Richard Z.,Sitkoff, Doree F.,Galella, Michael A.,Nirschl, David S.,Van Kirk, Katy,Miller, Arthur V.,Huang, Christine S.,Chang, Ming,Chen, Xue-Qing,Salvati, Mark E.,Wexler, Ruth R.,Lawrence, R. Michael
, p. 6162 - 6175 (2012/09/07)
A series of diphenylpyridylethanamine (DPPE) derivatives was identified exhibiting potent CETP inhibition. Replacing the labile ester functionality in the initial lead 7 generated a series of amides and ureas. Further optimization of the DPPE series for potency resulted in the discovery of cyclopentylurea 15d, which demonstrated a reduction in cholesterol ester transfer activity (48% of predose level) in hCETP/apoB-100 dual transgenic mice. The PK profile of 15d was suboptimal, and further optimization of the N-terminus resulted in the discovery of amide 20 with an improved PK profile and robust efficacy in transgenic hCETP/apoB-100 mice and in hamsters. Compound 20 demonstrated no significant changes in either mean arterial blood pressure or heart rate in telemeterized rats despite sustained high exposures.
